Cognitive function impairment of patients with treatment-resistant depression and its clinical treatments

Objective To evaluate the roles of multi-voxel proton magnetic resonance spectroscopy (1H-MRS) in the early diagnosis of vascular cognitive impairment no dementia (VCIND).Methods Seventy-eight out-patients and inpatients in Department of Neurology, the second Affiliated Hospital of Soochow University from December 2008 to September 2009 were recruited in this case-control study.Their cognitive functions were assessed with a wide range of neuropsychological battery of tests including Montreal cognitive assessment ( MoCA Beijing Version ), auditory verbal learning test ( AVLT), digital span test (DST), Rey-Osterrieth complex figure test (CFT) ,semantic and phonetic fluency tests, digit symbol coding subtest (DSCT), trail making test (TMT), clock drawing test (CDT) and the Stroop color-word test (SCWT).All patients were classified into vascular cognitive impairment no dementia (VCIND) group and cognitive normal control group based on the results of neuropsychological tests.Eighteen patients with VCIND and 18 gender-, age- and education-matched normal control were randomly selected for the following study.With multi-voxel 1H-MRS, the levels of N-acetylaspartartate (NAA), creatine (Cr) and choline (Cho) in gray matters of bilateral frontal lobe, temporal lobe, parietal lobe and thalamus were measured and the ratios of NAA/Cr, Cho/Cr were compared between the two groups.Meanwhile, the correlations between scores of MoCA and its sub-items and the ratios of NAA/Cr, Cho/Cr were analyzed in VCIND group.Informed consent was obtained from all participants and the study was approved by the Ethics Committee of the hospital.Results Compared with control group, the ratios of NAA/Cr were significantly decreased in bilateral gray matters of thalamus ( left, 1.56 ± 0.49 vs 1.89 ± 0.48, F = 11.222, P = 0.002; right,1.63± 0.45 vs 1.86 ± 0.33, F = 5.358, P = 0.027 ).No significant difference were found in NAA/Cr in gray matters of bilateral frontal lobe, temporal lobe, parietal lobe and Cho/Cr in all regions between two groups ( all P ＞ 0.05 ).In VCIND group, the decreased degree of NAA/Cr in bilateral gray matters of thalamus was significantly positively correlated with the MoCA total score ( r = 0.54, 0.44 ) as well as the sub-scores in tested items of memory ( r = 0.61, 0.49 ), attention ( r = 0.43, 0.36 ), language ( r = 0.39,0.31) and visuospatial or executive( r = 0.29 , 0.33, all P＜0.05 orP＜0.01).Conclusions Cognitive impairment in patients with VCIND maybe related to metabolic dysfunction of neurons in bilateral thalamic.Multi-voxel 1H-MRS plays an important role in early diagnosis and monitoring disease progression of VCIND. Key words: Cognitive disorders; Magnetic resonance spectroscopy; Cerebrovascular disorders; Neuropsychological tests

Cognitive Profiles in Treatment-Resistant Late-Life Depression and Their Impact on Treatment Outcomes

Oral ketamine for treatment resistant major depression – A double blind randomized controlled trial

Thioredoxin is not a marker for treatment-resistance depression but associated with cognitive function: An rTMS study

Treatment resistant depression can be very disabling and has a significant negative impact on a patient, their family or caregivers, and the society. There is a growing evidence on the efficacy and safety of ketamine for treatment resistant depression. Ketamine is a racemate consisting of esketamine and arketamine, is an N-methyl D-aspartate receptor antagonist and comes in different formulations and in fact intranasal ketamine is FDA-approved in the US. Despite the existing evidence and FDA approval for treatment resistant depression, data on older individuals remains limited. Late life depression especially those that are treatment resistant can be very disabling, with significant functional and cognitive impairments, increased morbidity and mortality, and the psychosocial burdens.This presentation describes outcomes for 2 cases of older individuals with treatment resistant depression who were treated with intranasal ketamine. One improved, and one did not. The scarce available literature of the use of ketamine in the geriatric population shows ketamine is well tolerated and effective. Remission rates in 3 separate show remission rates of 46.5%, 57% and 69.5% respectively. The discussion will include a review of the mechanism of action of ketamine as a novel antidepressant, the mixed evidence for its role in treatment resistant late life depression, and the practical and operational aspects relevant to running a ketamine clinic.

Objective To explore the influence of different degrees of obstructive sleep apnea hypopnea syndrome (OSAHS) associated on cognitive function. Methods 86 hospitailized patients with OSAHS diagnosis standard by our department polysomnography were collected.According to apnea hypopnea index (AHI), they were divided into the mild-moderate and severe groups.And then we compared two groups of Montreal cognitive assessment scale (MoCA) results, event related potential (ERP) ingredients in P300 latency period, the brain volume of hippocampal atrophy and cerebral white matter lesions related focal high signal around the lateral ventricle which measured by regular craniocerebral MRI sequence and perpendicular to the bilateral hippocampal fluid attenuated inversion recovery (FIAIR) sequence. Results The MoCA total score of the severe group was significantly lower than the moderate group′ and so did the scores of in memory′ attention′ execution′ability (P<0.05), but there was no significant difference in the rest of cognitive field.The P300 latency period of the severe group was significantly longer than the moderate group (P<0.05). With the severity of OSAHS aggravated, hippocampal volume atrophy and PVH showed a trend of increase, the severe group was significantly higher than the moderate group (P<0.05). Conclusions Compared with moderate patients′ the cognitive function of severe patients with OSAHS which is mainly reflected in the memory′ attention′ execution′ability, and its corresponding brain structure and function are affected at the same time, its can provide early and objective basis for OSAHS′ cognitive impairment diagnosis. Key words: Obstructive sleep apnea hypopnea syndrome; Cognitive impairment; Montreal cognitive assessment scale; P300 latency period; Hippocampus; White matter

Background: There is scanty report on the cognitive impairment and health status of the elderly in the sub-saharan African community. Objective: This study is to investigate the pattern of cognitive impairment and health morbidities among the elderly in a sub-Saharan African community. Methods: A household survey was conducted among 350 elders. They were interviewed with a questionnaire to ascertain their socio-demographic and health status information. Subsequently, the modified Mini-Mental State Examination [MMSE] was administered to elicit cognitive impairment based on cut-off score ≥13. Results: The mean MMSE score among participants was 20.7(±5.3) and about one-tenth of them 38(10.9%) had cognitive impairment. Of the study sample, 44% reported physical health morbidities; hypertension (23.2%), diabetes mellitus (10%) and visual impairment (5.4%) were the most frequently occurring morbidities. Cognitive impairment was associated with increasing age and most prevalent among the middle olds [70-79 years] ( p <0.001), while formal education seems protective ( p =0.022). Likewise, those with formal education were more likely to report medical illnesses ( p =0.004). Following logistic regression to control for effects of confounders, absence of formal education (Odd Ratio [OR] =0.465; 95% Confidence Interval [95%CI] =0.207-1.046) and increasing age ([OR] =6.617; 95%CI= 3.129- 13.993) were independent predictors of impairment in cognitive function. Conclusion: A high burden of cognitive impairment along with health morbidities was prevalent among the elderly; while increasing age and formal education were the identifiable determinants. Evolvement of public policies, health resource planning and service design to address geriatric health issues using age-related prioritization model are advocated. Similarly, the promotion of population literacy is indicated as it seems to have positive, long-lasting socioeconomic as well as health effects into old age. Further research is also justified. Keywords: Africa; Cognitive impairment; Health service; Morbidity; Public policy

Objective To investigate the cognitive impairment in depression with anxiety symptom and its influencing factors. Methods 458 first-episode depression patients were assessed with Hamilton Anxiety Scale (HAMA). According to the score of HAMA, the patients with depression were divided into with anxiety symptom group (n=266) and without anxiety symptom group (n=76). Using Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess neuropsychological function. Results (1)The group without anxiety symptom had higher scores on categories completed(2.88±2.14), learning to learned(64.16±24.20), immediately memory(81.78±17.16), visual span(84.08±15.41), attention(106.45±20.72) and delayed memory (86.12±13.06) than the group with anxiety symptom had((2.07±1.98), (54.33±27.05), (70.47±17.61), (79.76±14.63), ( 98.25±17.11), (79.97±16.10) respectively), and all these differences were significant (P<0.01 or P<0.05). The group without anxiety symptom had lower scores on response error(61.21±21.50), perseverative error percentage(17.11±6.10), monochrome time(19.04±6.57), time of meaning interference(15.01±9.11) and time of color interference(2.79±2.82) than the group with anxiety symptom had((67.20±21.87), (19.21±7.18), (21.03±7.69), (17.92±10.64), (3.86±5.61)respectively), and all these differences were significant (P<0.05). (2)The combination of educational years, age, somatic anxiety and psychic anxiety explained the 28.1% variances of immediately memory(F=25.015, P<0.01); the combination of educational years and psychic anxiety explained the 19.8% variances of delayed memory(F=31.625, P<0.01); and the combination of age and psychic anxiety explained the 13.6% variances of time of meaning interference(F=20.293, P<0.01). Conclusion Depression with anxiety symptom has more severe impairment on executive function, processing speed, memory and attention.Educational years, age, psychic anxiety and somatic anxiety are influencing factors. Key words: Depression; Anxiety symptom; Neuropsychological function

Introduction. This article aimed to investigate the effect of heat stress on cognitive performance and the blood concentration of stress hormones among workers of a foundry plant. Methods. Seventy workers within the exposed (35 people) and unexposed (35 people) groups were studied. The wet bulb globe temperature (WBGT) index was measured for heat stress assessment. The cognitive performance tests were conducted using the Stroop color word test (SCWT) before and during working hours. For the assessment of the serum level of cortisol and the plasma level of adrenaline and noradrenaline, blood samples were taken during working hours from both groups. Results. Only for SCWT III was there a significant relationship between heat stress and test duration, error rate and reaction time. The laboratory test results revealed significantly higher concentrations of cortisol, adrenaline and noradrenaline in the exposed subjects than in the unexposed group. There existed a positive correlation between cortisol, adrenaline, noradrenaline and WBGT index and also test duration and reaction time of SCWT III, and number of errors of SCWT I, SCWT II and SCWT III during work. Conclusion. Heat stress can lead to an increase in the blood level of stress hormones, resulting in cognitive performance impairment.

Objective To investigate the level of cognitive function and quality of life in patients with brain tumors, and to explore the correlation between cognitive function and quality of life. Methods A total of 116 patients with brain tumors hospitalized in a Class Ⅲ Grade A hospital in Shanghai from September 2017 to February 2018 were selected by convenience sampling method. General data questionnaire, Montreal Cognitive Assessment (MoCA) and Quality of Life Instruments for Cancer Patients-Head and Neck Cancer (QLICP-HN) were used in the investigation. Pearson correlation analysis was used for correlation analysis of normal distribution, and Spearman correlation analysis was used for correlation analysis of non-normal distribution. Results The total score of MoCA of the 116 patients was (23.9±3.9) , among which 66 patients (56.9%) got abnormal cognitive scores, and 50 patients (43.1%) got normal cognitive score. The total score of QLICP-HN was (66.6±6.8) , and there was a positive correlation between the total score of MoCA and QLICP-HN (r=0.318, P<0.01) . The total QLICP-HN score of normal cognitive function group (68.7±6.6) was higher than that of abnormal cognitive function group (64.9±6.6) . The difference was statistically significant (t=2.982, P=0.004) . Conclusions Multiple cognitive impairment is common in patients with brain tumors and affects their quality of life. Medical staff should pay more attention to the early evaluation of cognitive function in patients with brain tumors and take effective measures for rehabilitation training of cognitive function. Key words: Brain neoplasms; Cognition; Quality of life; Correlation

BackgroundAlthough post-stroke depression is a well-characterized disorder, there is less understanding of how pre-existence of depression is affected by a stroke.Case presentationWe describe a patient with treatment-resistant major depression, which had been ongoing for 14 years but disappeared shortly after onset of a subarachnoid hemorrhage. Her cognitive function and functional status were mostly unaffected by the stroke. However, she no longer excessively regretted past events. Lesions were found in the orbitofrontal cortex, which is involved in feeling regret, and in the adjacent subgenual cingulate area, which is metabolically hyperactive in treatment-resistant depression and is the target for deep-brain stimulation for relief of treatment-resistant depression. The lesions from the stroke may have caused the disappearance of the patient’s treatment-resistant depression by alleviating excessive regret and decreasing the elevated activity in these areas.ConclusionsThis patient’s clinical course may shed light on the neuropsychological and neurophysiological mechanisms of major depression of the melancholic subtype.

Magnetic seizure therapy (MST) has shown efficacy in adult patients with treatment-resistant depression with limited impairment in memory. To date, the use of MST in adolescent depression has not been reported. Here we describe the first successful use of MST in the treatment of an adolescent patient with refractory bipolar depression. This patient received MST in an ongoing open-label study for treatment-resistant major depression. Treatments employed a twin-coil MST apparatus, with the center of each coil placed over the frontal cortex (ie, each coil centered over F3 and F4). MST was applied at 100 Hz and 100% machine output at progressively increasing train durations. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale and cognitive function was assessed with a comprehensive neuropsychological battery. This adolescent patient achieved full remission of clinical symptoms after an acute course of 18 MST treatments and had no apparent cognitive decline, other than some autobiographical memory impairment that may or may not be related to the MST treatment. This case report suggests that MST may be a safe and well tolerated intervention for adolescents with treatment-resistant bipolar depression. Pilot studies to further evaluate the effectiveness and safety of MST in adolescents warrant consideration.

Deep brain stimulation (DBS) is a promising intervention for treatment-resistant depression (TRD). Effects on cognitive functioning are unclear since they have been studied in small samples. We aim to estimate the impact of DBS on cognitive functioning in TRD with a systematic review and meta-analyses. After systematically searching PubMed we included 10 studies which compared standardized neuropsychological tests before and after DBS or between active and sham DBS in TRD. Different random-effects meta-analyses were done for different cognitive (sub-)domains and for different follow-up time windows (<6 months, 6-18 months, and >18 months). We found no significant differences in cognitive functioning up to 6 months of DBS. After 6-18 months of DBS small to moderate improvements were found in verbal memory (Hedge's g = 0.22, 95% CI = [0.01-0.43], p = 0.04), visual memory (Hedge's g = 0.37, 95% CI = [0.03-0.71], p = 0.04), attention/psychomotor speed (Hedge's g = 0.26, 95% CI = [0.02-0.50], p = 0.04) and executive functioning (Hedge's g = 0.37, 95% CI = [0.15-0.59], p = 0.001). Not enough studies could be retrieved for a meta-analysis of effects after >18 months of DBS or for the comparison of active and sham DBS. Qualitatively, generally no differences in cognitive functioning between active and sham DBS were found. No cognitive decline was found in this meta-analysis up to 18 months of DBS in patients with TRD. Results even suggest small positive effects of DBS on cognitive functioning in TRD, although this should be interpreted with caution due to lack of controlled data.

Objectives - Age-related decline in cognitive functions is a common phenomenon but not uniform across all domains and varies amongst individuals. Few longitudinal studies have demonstrated the relation between elevated blood pressure and fall in cognitive function, but Indian literature in this regard is scarce. Hence, we conducted this study to determine the prevalence and occurrence of cognitive deficits in hypertensive patients, and its relation with socio-economic status. Methods - This was a two-arm cross-sectional study. 100 patients (hypertensives and normotensives) attending geriatric/medicine out-patient department of a tertiary care centre were recruited. Grading of hypertension was done and details of medication were taken. Presence of psychiatric/neurological complications were noted. Socio-economic status of patients was assessed using Modified Kuppuswamy’s Socioeconomic Scale. Two established psychiatric evaluations namely Addenbrooke’s Cognitive Examination (ACE) and Trail Making Test (TMT) were conducted. Results - Forgetfulness, the most common complaint, was presented by 44% cases but only by 10% controls. Amongst the hypertensives 13 patients had confusion, 2 had aggressive behaviour and 15 had behavioural changes. 94% cases had cognitive impairment in test group compared to 72% in control, by the ACE. The difference in time lag for TMT Part A between cases and controls was statistically significant (P<0.05). For TMT Part B, difference was not significantly different. ACE scores in hypertensives of lower socioeconomic status was significantly less (P<0.05). Conclusion - Assessment revealed significantly high prevalence of cognitive impairment in hypertensives as compared to normotensives. Early identification of cognitive dysfunction may provide considerable benefit to hypertensive patients.

Objective To study the variation characteristics of cognitive impairment and its influencing factors using telephone interview for cognitive status-modified(TICS-m)in patients after cerebral ischemia, and evaluate the application value of TICS-m. Methods Ninety-five patients with cerebral ischemia, matched the criteria and admitted to our hospital from December 2014 to December 2015, were chosen. Their related information was recorded, their cognitive function was assessed by face-to-face neuropsychological tests, including Montreal Cognitive Assessment(MoCA), Hamilton Depression Rating Scale, activities of daily living(ADL)and Chinese Neuropsychiatric Inventory(CNPI), in the acute stage(10-14 d), and then, their cognitive function was assessed by TICS-m 4, 12 and 18 weeks after cerebral ischemia and their rehabilitation was followed up. Results The incidence of cognitive impairment after cerebral ischemia in the acute stage was 78.9%; when cutoffs of dementia was <28 points and mild cognitive impairment(MCI)was 28-33 points in TICS-m, the incidences of cognitive impairment 4, 12 and 18 weeks after cerebral ischemia were 69.4%(MCI: 45.8%, dementia: 23.6%), 57.3%(MCI: 42.6%, dementia: 14.8%), 44.9%(MCI: 34.7%, dementia: 10.2%). And the TICS-m total scores 12 and 18 weeks after cerebral ischemia were significantly increased than that 4 weeks after cerebral ischemia, amplification reaching to 7.9% and 10.7%(P<0.05); subtests analysis indicated that 12 and 18 weeks after cerebral ischemia, the memory recovered obviously: the scores were significantly increased, amplification reaching to 34.5% and 49.0% as compared with those 4 weeks after the cerebral ischemia(P<0.05). Logistic regression analysis indicated that age(OR=66.615, P= 0.001, 95% CI: 5.449-814.349), education level(OR=0.134, P=0.009, 95% CI: 0.029-0.608)and work type(OR=0.090, P=0.004, 95%CI: 0.017-0.464)were closely related to the cognitive impairment after cerebral ischemia. The follow-up visit analysis showed that most patients(91.8%)could take the drug for the secondary prevention of stroke and return to the clinic regularly, and only a small part of patients(31.8%)took the related drugs to improve their cognitive impairment; about 77.6% patients recovered good after discharge, 54.7% patients supported and hoped the doctors continue the follow-up visit by telephone. Conclusions The incidence of cognitive impairment is high after cerebral ischemia and it declines over time, and advanced age, low education level and manual work are the important factors affect the incidence. TICS-m is an effective and convenient tool to assess the characteristic and prognosis of patients with cognitive impairment after the cerebral ischemia, and it' s suitable for clinic follow-up study and scientific research. Key words: Telephone interview for cognitive status-modified; Cerebral ischemia; Cognitive function